P087 Contributions of monocytes to gut inflammation in acute and chronic colitis models

1University Hospital Muenster, Department of General and Visceral Surgery, Muenster, Germany,2Louisiana State University Health Sciences Centre-Shreveport, Department of Molecular & Cellular Physiology, Shreveport, Louisiana, United States,3Louisiana State University Health Sciences Centre-Shreveport, Department of Microbiology and Immunology, Shreveport, Louisiana, United States,4Louisiana State University Health Sciences Centre-Shreveport, Centre of Excellence for Arthritis and Rheumatology, Shreveport, Louisiana, United States

Background

Monocytes and macrophages play major roles in the pathogenesis of inflammatory bowel diseases (IBD). In addition to contributing to inflammation, these cells possess anti-inflammatory properties, including tissue repair, initiation of inflammation-associated lymphangiogenesis and mucosal healing. We evaluated contributions of monocytes/macrophages to acute and chronic colitis using animal models, where monocytes were depleted at onset, progression, or recovery phases of experimental colitis.

Results

Compared with WT mice, DT-treated CCR2-DTR mice showed significantly fewer lamina propria Ly6Chigh monocytes in all models. When monocytes were depleted at the onset of intestinal inflammation (anti-CD40 colitis), we observed a significant protection as seen in attenuated histopathology and reduced inflammatory mediators. When monocytes were depleted during established T-cell mediated colitis, we observed protection against injury with reductions in colonic inflammatory chemokine and cytokine levels. However, when monocytes were depleted during the recovery phase of DSS-induced colitis, we found no differences in colonic histopathology, chemokine, or cytokines levels.

Conclusion

We showed that monocytes/macrophages play multifaceted effector roles in intestinal inflammation. Whereas their presence contributes to development and perpetuation during active disease, myeloid cells also make protective contributions to the recovery and healing phases following intestinal injury. These results indicate that monocytes/macrophages targeting approaches must be carefully balanced to limit their pro-inflammatory role while preserving beneficial effects of these cells on limiting inflammatory processes and restoring tissue homeostasis.